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991.
The objective of the present study is to improve iron bioavailability using high-density gastroretentive pellets of zero valent iron nanoparticles (ZVINPs). ZVINPs were prepared by the chemical reduction method and were characterized for surface morphology, surface charge, and thermal properties. High-density gastroretentive pellets of iron nanoparticles were prepared using spheronization technique. Pellets were characterized for its micromeritic properties, in vitro drug release, and ex vivo permeability. The pharmacokinetic parameters, organ distribution, and toxicity of the optimized pellets were investigated in Wistar rats. In vivo results revealed more than 2-fold increases in oral bioavailability of iron by pellets compared to plane ferrous sulfate. Toxicological studies of the carriers indicated no evidence of liver damage in acute treatment; however, few complications were observed in chronic treatment groups. These results indicated that ZVINPs pellets successfully improve the oral iron bioavailability but need to obtain more information on repeated dose toxicity to initiate the clinical evaluation of investigational products. 相似文献
992.
Rohini Sharma Lars Wilkinson Hrvoje Vrazic Evan Popoff Sandra Lopes Steve Kanters 《Current medical research and opinion》2018,34(9):1595-1603
Objective: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.Methods: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.Results: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0?mg and 0.5?mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA1c for once-weekly semaglutide 1.0?mg vs SGLT-2is ranged from ?0.66% for canagliflozin 300?mg (95% Credible Intervals [CrI]: ?0.82, ?0.50%) to ?1.11% for dapagliflozin 5?mg (95% CrI: ?1.37, ?0.85%). Once-weekly semaglutide 1.0?mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.Conclusion: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy. 相似文献
993.
Michelle Z. Dion Danielle Leiske Vikas K. Sharma Christina L. Zuch de Zafra Cleo M. Salisbury 《Pharmaceutical research》2018,35(11):222
Purpose
Biotherapeutics can be susceptible to oxidation during manufacturing and storage. Free L-methionine is known to protect methionine residues in proteins from oxidation. Similarly, free tryptophan and other indole derivatives have been shown to protect tryptophan residues from oxidation. N-acetyl-DL-tryptophan was previously identified as a potentially superior antioxidant to tryptophan as it has a lower oxidation potential and produces less peroxide upon light exposure. This study sought to confirm the antioxidant efficacy and safety of N-acetyl-DL-tryptophan and L-methionine as formulation components for biotherapeutic drugs.Methods
Antibodies were subjected to AAPH and light exposure in the presence of N-acetyl-DL-tryptophan and L-methionine. Oxidation in relevant CDR and Fc residues was quantified by peptide map. In silico, in vitro, and in vivo studies were performed to evaluate the safety of N-acetyl-DL-tryptophan and L-methionine.Results
Peptide mapping demonstrated that N-acetyl-DL-tryptophan was effective at protecting tryptophans from AAPH stress, and that the combination of N-acetyl-DL-tryptophan and L-methionine protected both tryptophan and methionine from AAPH stress. The safety assessment suggested an acceptable safety profile for both excipients.Conclusions
N-acetyl-tryptophan and L-methionine effectively reduce the oxidation of susceptible tryptophan and methionine residues in antibodies and are safe for use in parenteral biotherapeutic formulations.994.
Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes
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Kusum Vats Drishty Satpati Rohit Sharma Chandan Kumar Haladhar Dev Sarma Sharmila Banerjee 《Journal of labelled compounds & radiopharmaceuticals》2018,61(2):68-76
The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG2‐c(NGR), were synthesized, radiolabeled with 99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. 相似文献
995.
Non‐peptide‐based new class of platelet aggregation inhibitors: Design,synthesis, bioevaluation,SAR, and in silico studies
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Pradeep K. Jaiswal Vashundhra Sharma Surendra Kumar Manas Mathur Ajit K. Swami Dharmendra K. Yadav Sandeep Chaudhary 《Archiv der Pharmazie》2018,351(3-4)
996.
Synthesis,molecular docking,and pharmacological evaluation of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents
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997.
Adherence to Canada's Food Guide recommendations among Alberta's multi‐ethnic youths is a major concern: findings from the WHY ACT NOW project
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F. Kolahdooz F. Nader M. Daemi S. L. Jang N. Johnston S. Sharma 《Journal of human nutrition and dietetics》2018,31(5):658-669
Background
Dietary habits formed during youth may result in the development of obesity and chronic diseases in adulthood. We aimed to determine the frequency of the consumption of foods and beverages and the degree of adherence to Canada's Food Guide recommendations among multi‐ethnic youths.Methods
Participants were recruited from 12 schools in the Edmonton, Alberta area by use of posters, school newsletters and advertisements. A 30‐item food frequency questionnaire was administered by a trained interviewer to assess dietary intake in a convenience sample of 557 (328 females and 229 males) youths aged 11–23 years; for the purpose of the present study, only the 14–18 years age group was considered in the analysis. Participants were divided by sex and self‐identified ethnicity into four groups [Indigenous, African & Middle Eastern (AME ), Asian, and European]. Statistical analysis of the data was undertaken using t ‐tests, Welch's analysis of variance and Games‐Howell tests. P < 0.05 was considered statistically significant.Results
Vegetables and Fruit recommendations were the least likely to be followed, with 90.7–96.8% of participants in all groups not consuming the recommended number of servings day–1. The mean frequency of fruit consumption was lower among Indigenous youths compared to Asian youths (0.90 versus 1.37 times day–1). A greater proportion of males than females (55.9% versus 44.3%) did not meet the minimum recommendations for Meat and Alternatives (P = 0.016). The percentage of youths not adhering to recommendations for Milk and Alternatives was 81.7% for Indigenous, 73.3% for AME , 78.6% for Asian and 63.5% for European youths. Indigenous youths more frequently consumed potato chips and soft drinks compared to other ethnic youths. The most frequently consumed beverage was milk (1.25 times day–1).Conclusions
The majority of youths did not consume minimum daily recommended servings of Vegetables and Fruit, Milk and Alternatives, and/or Meat and Alternatives food groups. Evidence‐based dietary interventions and public health strategies are needed.998.
999.